Urologic Medications

Question 1

What is the pathophysiology of BPH?

Answer 1

Smooth muscle and epithelial cell proliferation in the prostatic transition zone. This leads to an enlarged gland increasing the resistance to urinary flow.

Question 2

What are the pharmacological principles of treating symptomatic BPH?

Answer 2

1. Decreasing prostatic muscular tone (alpha -blockers)

2. Decreasing prostatic size (ARI’s)

Question 3

What receptor is targeted to decrease smooth muscle tone in the prostate?

Answer 3

Alpha-1 Adrenoreceptor (heavily concentrated in the prostatic urethra, stroma, and bladder neck region.

Question 4

What mechanism facilitates prostate growth?

Answer 4

Prostate growth controlled by testosterone and its conversion to DHT by two isoenzymes: 5-alpha-reductase type I and 5-alpha reductase type II. Growth is driven by 5-ARI type II( more of this enzyme present in prostate)

Question 5

What are the relative concentrations of 5-alpha reductase type I and type II in the prostate?

Answer 5

5-alpha reductase type I is present in only 10% of the prostate and 5-alpha reductase type II is much more prevalent within the prostate.

Question 6

How are alpha blockers subdivided?

Answer 6

By their selectivity for the alpha-1 adrenoreceptor. (first generation least selective , second generation slightly more selective, third generation most selective)

Question 7

What are examples of first generation alpha blockers and why are they not recommended as therapy for BPH?

Answer 7

Phentolamine and phenoxybenzamine - large side effect profile given non-selectivity: palpitations, dizziness, impaired ejaculation, nasal congestion and visual disturbances)

Question 8

What are examples of second generation alpha blockers and which are okay to use for BPH and which are not?

Answer 8

Prazosin (minipress) - NOT RECOMMENDED (worst side effect profile), Doxazosin (Cardura), Terazosin (hytrin) - side effects include hypotension and dizziness and BP monitoring is required

Question 9

What are examples of third generation alpha blockers?

Answer 9

Tamsulosin (flomax), alfuzosin (xatral), sildosin (rapaflo) - these have the least cardiovascular side effects.

Question 10

What is intraoperative floppy iris syndrome (IFIS)?

Answer 10

side effect of alpha blockers in men undergoing cataract surgery - due to alpha-1 adrenoreceptor in iris leading to increased surgical complication in cataract surgery.

Question 11

What are the current recommendations concerning alpha blockers for symptomatic BPH and IFIS

Answer 11

1) All alpha blockers can causes IFIS but more likely with “selective” alpha blockers
2) Patients taking alpha blockers should inform their ophthalmologist before eye surgery
3) Patients with cataracts should be informed about the risks with alpha blockers and should consider having surgery prior to commencing therapy.
4) Ophthalmologic evaluation is recommended in patients with a history of cataracts or decreased vision prior to starting alpha blockers
5) Discontinuation of tamsulosin prior to surgery did not reduce severity of IFIS in a prospective trial

Question 12

What are common side effects of alpha blockers?

Answer 12

1. Syncope
2. Lightheadedness
3. Headache
4. Rhinitis
5. Ejaculatory dysfunction
6. Tachycardia

Question 13

What two medications are used to decrease the prostate size and what isoenzymes do they target?

Answer 13

Dutasteride (Avodart) and finasteride (Proscar)

Dutasteride - blocks both type I and type II 5-alpha-reductase

Finasteride is selective for type I 5-alpha-reductase